Yttrium-90 SIRT plus atezolizumab/bevacizumab in unresectable huge HCC (>10 cm): A multicenter retrospective study.

4144 Background: Huge hepatocellular carcinoma ((huge HCC, ≥ 10 cm)) has poor prognosis with limited systemic therapy efficacy. We evaluated Y-90 selective internal radiation therapy (SIRT) combined with atezolizumab plus bevacizumab (Atezo/Bev) in this population. Methods: This retrospective multicenter study enrolled 21 patients with unresectable huge HCC (maximum diameter >10 cm) treated with Y-90 SIRT plus Atezo/Bev from January 2023 to July 2025. Eligibility criteria included Child-Pugh class A/B, ECOG performance status 0/1, and completion of ≥2 treatment cycles. The primary endpoint was ORR assessed by mRECIST. Secondary endpoints: PFS, OS, and safety (CTCAE v5.0). Results: Among the patients median tumor diameter 116.2 mm (IQR 105.6-131.9); >15 cm 14.3%; BCLC C 76.2%; PVTT 76.2%; extrahepatic metastasis 23.8%. The objective response rate (ORR) was 61.9% (13/21), including 6 (28.6%) complete responses (CR) and 7 (33.3%) partial responses (PR). The disease control rate (DCR) was 76.2% (16/21), with 3 (14.3%) stable disease (SD) and 5 (23.8%) progressive disease (PD). Median follow-up 11.0 months (IQR 7.1-25.0). Respectively, the median OS was not reached, at data cutoff, the 6- and 12-month PFS rates were 65.1% and 27.1%, respectively. The 6-, 12-, and 24-month OS rates were 76.2%, 57.5%, and 49.3%. Radiological responders (CR/PR) showed reduced progression risk (HR 0.46; 95% CI 0.16-1.32) and death risk (HR 0.41; 95% CI 0.11-1.49) vs non-responders. Nonrim APHE correlated with improved survival (median OS: 18.0 vs 8.0 months; HR 0.54). Grade ≥3 treatment-related adverse events occurred in 14.3% (3/21): pneumonia (n=2), hepatic encephalopathy (n=1). No treatment-related deaths. Conclusions: In this cohort, Y-90 SIRT plus Atezo/Bev achieved 61.9% ORR with manageable toxicity. These findings warrant prospective trials. Baseline characteristics and clinical outcomes (N=21). Characteristic Value Age, median (range), years 53 (28–76) Male sex, n (%) 18 (85.7) ECOG performance status 0/1, n (%) 16 (76.2) / 5 (23.8) Etiology HBV/Alcohol/Unknown, n (%) 18 (85.7) / 1 (4.8) / 2 (9.5) Tumor diameter, median (IQR), mm 116.2 (105.6–131.9) Tumor >15 cm, n (%) 3 (14.3) BCLC stage A/B/C, n (%) 4 (19.0) / 1 (4.8) / 16 (76.2) Child-Pugh A/B, n (%) 17 (81.0) / 4 (19.0) Portal vein tumor thrombus, n (%) 17 (81.0) Extrahepatic metastasis, n (%) 5 (23.8) AFP >400 ng/mL, n (%) 10 (47.6) Complete responses (CR) 6 (28.6%) Partial responses (PR) 7 (33.3%) Stable disease(SD) 3 (14.3%) Progressive disease (PD) 5 (23.8%) Objective response rate (ORR) 61.9% (13/21) Disease control rate (DCR) 76.2% (16/21) Median follow-up, months 11.0(IQR 7.1-25.0) 6- and 12-month PFS rates 65.1% and 27.1% 6-, 12-, and 24-month OS rates 76.2%, 57.5%, and 49.3% Grade ≥3 TARE 14.3% (3/21) TARE: treatment-related adverse events.